Pharmacokinetics of Tipranavir Soft Elastic Capsules (SEDDS) and Ritonavir and Their Effects on Cytochrome P-450 (3A4) in Healthy Volunteers

NCT02251132 | Completed Phase 1

• 1 other identifier: 1182.5
• Study Type: interventional
• Target: 113
• Locations: 0 countries
• Sites: N/A

Brief Summary

The objective of this study is to establish the tipranavir-ritonavir steady-state dose-exposure relationships when administered on a b.i.d. dosing regimen; to determine the effects of tipranavir (TPV) and ritonavir (RTV) on cytochrome P-450 (CYP3A4) activity; to establish the dependency of the TPV M1 metabolite on RTV co-administration. Additionally, the short-term safety and tolerance of this drug combination will be evaluated.

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• Trough plasma concentration at steady state (Cmin,ss)

  up to 24 hours

• Maximum plasma concentration at steady state (Cmax,ss)

  up to 24 hours

• Time of maximum concentration (tmax)

  up to 24 hours

• Area under the plasma concentration time curve from 0 to 12 hours (AUC0-12)

  up to 12 hours

Secondary Outcomes (5)

• Oral clearance (Cl/F)

  up to 24 hours

• Apparent terminal half life (t1/2)

  up to 24 hours

• Percent of erythromycin metabolized per hour

  up to 24 hours

• Number of subjects with clinically significant findings in laboratory tests

  up to 32 days

• Number of subjects with adverse events

  up to 32 days

Study Arms (8)

TPV/RTV Low 1

EXPERIMENTAL

Drug: TPV low 1; Drug: Ritonavir high; Drug: Radiolabelled erythromycin

TPV/RTV Low 2

EXPERIMENTAL

Drug: TPV low 2; Drug: RTV low; Drug: Radiolabelled erythromycin

TPV/RTV Low 3

EXPERIMENTAL

Drug: TPV low 2; Drug: Ritonavir high; Drug: Radiolabelled erythromycin

TPV/RTV Medium 1

EXPERIMENTAL

Drug: TPV medium; Drug: RTV low; Drug: Radiolabelled erythromycin

TPV/RTV Medium 2

EXPERIMENTAL

Drug: TPV medium; Drug: Ritonavir high; Drug: Radiolabelled erythromycin

TPV/RTV High 1

EXPERIMENTAL

Drug: TPV high 1; Drug: RTV low; Drug: Radiolabelled erythromycin

TPV/RTV High 2

EXPERIMENTAL

Drug: TPV high 1; Drug: Ritonavir high; Drug: Radiolabelled erythromycin

TPV/RTV High 3

EXPERIMENTAL

Drug: TPV high 2; Drug: Ritonavir high; Drug: Radiolabelled erythromycin

Interventions

TPV low 1 DRUG

TPV/RTV Low 1

TPV low 2 DRUG

TPV/RTV Low 2; TPV/RTV Low 3

TPV medium DRUG

TPV/RTV Medium 1; TPV/RTV Medium 2

TPV high 1 DRUG

TPV/RTV High 1; TPV/RTV High 2

TPV high 2 DRUG

TPV/RTV High 3

RTV low DRUG

TPV/RTV High 1; TPV/RTV Low 2; TPV/RTV Medium 1

Ritonavir high DRUG

TPV/RTV High 2; TPV/RTV High 3; TPV/RTV Low 1; TPV/RTV Low 3; TPV/RTV Medium 2

Radiolabelled erythromycin DRUG

TPV/RTV High 1; TPV/RTV High 2; TPV/RTV High 3; TPV/RTV Low 1; TPV/RTV Low 2; TPV/RTV Low 3; TPV/RTV Medium 1; TPV/RTV Medium 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female between 18 and 75 years of age inclusive
• Female subjects of child-bearing potential are required to use a barrier contraceptive method for at least 3 months prior to administration of study medication, during study medication administration and for 30 days after the end of the study
• Ability to swallow numerous large capsules without difficulty
• A body mass index (BMI) between 19 and 29 kg/m2
• Signed informed consent prior to trial participation
• Reasonable probability for completion of the study
• Acceptable screening laboratory values that indicate adequate baseline organ function are required at the time of screening. Laboratory values are considered to be acceptable if severity is no higher than Grade 1 based on the AIDS Clinical Trials Group (ACTG) Grading Scale. All laboratory values \> Grade 1 are subject to approval by the BIPI clinical monitor
• Acceptable medical history, physical examination, electrocardiogram, and chest X-ray are required prior to entering the treatment phase of the study
• Willingness to abstain from alcohol for 48 hours prior to study Day 0 and abstain from alcohol for the duration of the study
• Willingness to abstain from ingesting grapefruit or grapefruit juice for the duration of the study
• Urine drug screen negative for drugs of abuse
• Negative HIV serology
• Negative for Hepatitis B surface antigen and Hepatitis C antibody

You may not qualify if:

• Female subjects who:
• have a positive serum pregnancy test at Visits 1 or 2 OR
• are breastfeeding
• Receipt of any other investigational medicine for 30 days prior to Day 0
• Receipt of any known enzyme altering drug for 30 days prior to Day 0, grapefruit and grapefruit juice within 15 days prior to Day 0 and antibiotics within 10 days prior to Day 0
• Excessive cigarette smoking, defined as greater than 10 cigarettes per day
• Blood or plasma donation within 30 days prior to Day 0
• Subjects with a seated systolic blood pressure either \< 100 mg Hg or \> 150 mm Hg; resting heart rate either \< 50 beats/min or \> 90 beats/min
• Subjects with a history of any illness or allergy that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering tipranavir or ritonavir to the subject
• Subjects who have had an acute illness within 2 weeks prior to Day 0
• Subjects who are currently taking any over-the-counter drug within 7 days prior to Day 0, or who are currently taking any prescription drug that, in the opinion of the investigator in consultation with the BIPI medical monitor and pharmacokineticist, might interfere with either the absorption, distribution or metabolism of the test substances
• Hypersensitivity to tipranavir, ritonavir or sulfonamide containing drugs
• Evidence of active substance abuse that, in the investigator's opinion, could affect study adherence

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2014
• First Posted: September 29, 2014
• Study Start: October 1, 2000
• Primary Completion: December 1, 2000
• Last Updated: September 29, 2014

Record last verified: 2014-09